Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

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Abstract

The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

Original languageEnglish (US)
Pages (from-to)1241-1249
Number of pages9
JournalMolecular Cell
Volume9
Issue number6
DOIs
StatePublished - 2002

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p38 Mitogen-Activated Protein Kinases
Peptides
Catalytic Domain
Lip
Phosphotransferases
Phosphorylation
Enzymes

ASJC Scopus subject areas

  • Molecular Biology

Cite this

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title = "Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b",
abstract = "The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the {"}CD{"} domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.",
author = "Chang, {Chung I.} and Xu, {Bing E.} and Radha Akella and Cobb, {Melanie H.} and Goldsmith, {Elizabeth J.}",
year = "2002",
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language = "English (US)",
volume = "9",
pages = "1241--1249",
journal = "Molecular Cell",
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T1 - Crystal structures of MAP kinase p38 complexed to the docking sites on its nuclear substrate MEF2A and activator MKK3b

AU - Chang, Chung I.

AU - Xu, Bing E.

AU - Akella, Radha

AU - Cobb, Melanie H.

AU - Goldsmith, Elizabeth J.

PY - 2002

Y1 - 2002

N2 - The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

AB - The structures of the MAP kinase p38 in complex with docking site peptides containing a φA-X-φB motif, derived from substrate MEF2A and activating enzyme MKK3b, have been solved. The peptides bind to the same site in the C-terminal domain of the kinase, which is both outside the active site and distinct from the "CD" domain previously implicated in docking site interactions. Mutational analysis on the interaction of p38 with the docking sites supports the crystallographic models and has uncovered two novel residues on the docking groove that are critical for binding. The two peptides induce similar large conformational changes local to the peptide binding groove. The peptides also induce unexpected and different conformational changes in the active site, as well as structural disorder in the phosphorylation lip.

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